Clinical Value of Minimal Residual Disease Assessed by Multiparameter Flow Cytometry in Amyloid Light Chain Amyloidosis

Purpose: To assess the feasibility and prognostic value of minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in newly diagnosed amyloid light chain (AL) amyloidosis.Methods: Clinical data from 25 consecutive newly diagnosed AL amyloidosis patients with MRD data tested at 3 months after first-line therapy completion were retrospectively analysed in a single centre from 2012 to 2019. First-line therapy included 8 courses of VD or 4 courses of VD plus sequential autologous stem cell transplantation (ASCT), both without maintenance therapy.Results: Of 25 patients with very good partial response (VGPR) or better, 19 (76%) achieved MRD negativity. Baseline characteristics were not different between MRD-negative and MRD-positive patients. More ASCT patients than non-ASCT patients (90.0% vs 53.3%, P＝0.043) achieved MRD negativity. In the MRD-negative and MRD-positive groups, cardiac response was observed in 93% and 25% (P=0.019) and any organ response in 94% and 50%, respectively (P=0.023). At a median follow-up of 25.1 months, MRD-negative patients showed significantly longer progression-free survival (PFS) from diagnosis than MRD-positive patients (24.52 vs 76.39 months, P=0.004).Conclusions: MRD negativity measured by MFC at 3 months after first-line therapy completion in patients with AL amyloidosis is measurable and associated with improved organ response rates and PFS over a long follow-up.

Reconciliation of Time Perspectives as a Criterion for Therapy Completion

Summary Giancarlo Trombini presents the continuation of his research on the question of which criteria can be used to assess the progress of therapy in an objectively verifiable way and to make the decision on the completion of therapy. In the first phase of his research, the phenomenological criterion of a qualitative change in the patient’s relations toward the positive and higher complexity was proposed for this purpose. In terms of the working method in analytic therapy, this meant concretely: attention should be paid to what development is shown in the comparison of the relationships that occur in the dream narrative and in the subsequent associations. This criterion was therefore given the name manifest dream/association comparison (MDAC)—comparison between the manifest dream and the subsequent associations. The idea can easily be transferred to those therapy methods, which do not primarily work with reports of dream memories and subsequent associations—also, in other ways of working, it is possible to pay attention, in the way suggested by Trombini, to the qualitative development of the relationships which are thematized by the clients in the course of an hour. To this first criterion, another phenomenological criterion is now added in the present article: that of the “concluding therapeutic turn” (CTT). If the patient’s development reaches this turn in the course of the therapy in one session, this indicates, according to Trombini, that the therapy can soon be concluded. The fulfillment of this criterion can be recognized by the fact that in the sequence of dream narration and subsequent associations in a session, a relational dynamic toward the positive and higher complexity becomes recognizable and that is, at the same time, connected with a reconciliation of the three temporal reference systems (past, present, and future). The achievement of this CTT indicates that the patient is aware of the changes made in therapy and makes it evident to the therapist that the therapy is nearing completion.

NCOG-63. PEDIATRIC NEURO-ONCOLOGY SURVIVOR IDENTITY: A PROJECT REACH STUDY

BACKGROUND The degree to which adults treated for pediatric CNS tumors identify with cancer and survivorship, and factors influencing their identification, have been understudied. METHODS Self-reported data was collected from Project REACH, a locally-treated childhood cancer survivor cohort. Data included demographic (age, gender, race/ethnicity, marriage, education, employment, living situation, insurance), clinical (diagnosis, treatment), neurocognitive (CCSS NCQ), quality-of-life (QOL; SF-12, FACT-G) and survivorship identity variables. Participants were ≥ 18 years old, ≥ 2 years from diagnosis, and ≥ 1 year from therapy completion. RESULTS 132 participants; 59 males, and 118 non-Hispanic whites were included. Mean age at diagnosis and survey was 9.6 (range 0-22) and 26.7 (range 18-46) years, respectively. Treatment was diverse; 34% of participants received surgery only, 34% received surgery, chemotherapy, and radiation, and 32% received other treatment combinations. Most participants (67%) reported their cancer had “moderate,” “great,” or “total” effect on their current identity, and most (66%) thought of their diagnosis ≥ 1-2 times per month. A large proportion of survivors (83%) reported identifying as a “survivor.” Demographic and clinical variables were largely unelated to perceived effects of cancer, except for current age and QOL; 87% of survivors older than 30 reported moderate to great/total effect of cancer on their identity vs 51% of survivors age 18-21 (p=0.031). Participants reporting great/total effect on their identity had lower mental and physical health scores (SF-12) than those who reported no impact (48.5 vs 52.8, p=0.04; 42.6 vs 47.2, p =0.02 respectively). CONCLUSION The majority of participants report a significant impact from their childhood tumor diagnosis on their adult identity, and frequent diagnosis-related thoughts. Older survivors and those with poor QOL report greater effects on their identity. Interventions are needed to promote opportunities to make meaning of the pediatric CNS tumor experience as a way of achieving better quality of life.

Treatment patterns of advanced or recurrent endometrial cancer following platinum-based therapy in the US real-world setting.

e18036 Background: Following disease progression on or after primary (1L) platinum-based therapy (PBT) for advanced/recurrent (A/R) endometrial cancer (EC), patient (pt) prognosis is poor and no consensus on standard second-line therapy exists. This retrospective analysis aimed to understand real-world (RW) treatment patterns of pts with A/R mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC who progressed after 1L PBT. Methods: Physicians in Cardinal Health’s Oncology Provider Extended Network submitted retrospective data by abstracting outpatient electronic medical records of pts who received systemic treatment for A/R EC following PBT from 2016 to 2018. Demographics, clinical characteristics, treatments received, and outcomes were summarized descriptively. Results: This study included 84 pts with A/R dMMR/MSI-H EC (table). The majority of participating physicians were hematologists/medical oncologists (80%) and practiced in the community setting (70%). Median duration of therapy (mDOT) in 1L was 4.9 months (95% CI, 4.47–5.57); 64% of pts discontinued treatment due to therapy completion and 35% due to disease progression. In contrast, mDOT in 2L was 6.2 months (95% CI, 5.40–6.37); 37% of pts discontinued treatment due to therapy completion and 44% due to disease progression. The most common MMR/MSI testing modalities were next-generation sequencing (NGS) only, immunohistochemistry (IHC) only, and polymerase chain reaction (PCR) only (table). Conclusions: RW treatment patterns in pts with A/R dMMR/MSI-H EC show that most will undergo PBT retreatment. However, progression is the main reason for discontinuation during retreatment. An urgent need exists for durable therapies that improve prognosis. Opportunities to improve timely testing of MMR/MSI exist. [Table: see text]

PRINT: Prostate cancer intensive, non-cross reactive therapy for CRPC—Early observations of efficacy.

e17575 Background: Optimal sequencing of therapeutic agents in mCRPC remains debated, but the standard approach is to treat with one agent until resistance is met before switching. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat intrinsic heterogeneity, delay or prevent drug resistance, and minimize treatment toxicity. Methods: Patients received treatment with 3 consecutive treatment modules, each lasting 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 50 kBq/kg IV q4 weeks (in those with bone metastases). Upon completion of the 9-month regimen, patients are followed on ADT alone. Primary endpoint for the study is PSA or radiographic time to progression (TTP). Results: From 3/2017 to 1/2020, 38 of 40 planned men with mCRPC were enrolled, 28 patients have completed the 9-month study regimen and evaluable for TTP analysis. With median follow up of 54+ weeks, median time to PSA progression after therapy completion is 14.7+ weeks (95%CI; 5.5-23.9+ weeks). PSA response rates showed successive improvements with each sequential treatment module (Table). Eight patients (21.1%) continue on post-study surveillance with ADT alone, two of which have remained off any mCRPC agents for over a year (82+ weeks, 79+ weeks). In patients needing to restart therapy, experience with efficacy and tolerability of each agent while on the study, has helped inform subsequent mCRPC drug selection. The study regimen is well-tolerated, with few grade 3/4 AE’s: hyperglycemia (15.8%), diarrhea (5.3%), anemia (2.6%), fatigue (2.6%), neutropenia (2.6%), and thrombocytopenia (2.6%). Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen demonstrates significant antitumor benefits, with potential for long-term suppression of disease. Further longitudinal follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160 . [Table: see text]

Изучение терапевтической эффективности препарата Алфлутоп на модели открытого перелома бедренной кости у крыс

Введение. Клиническое применение гликозаминогликанов предотвращает разрушение макромолекулярных структур интерстициальной ткани и тканей суставного хряща, стимулирует процессы восстановления и обладает противовоспалительным действием. Эти эффекты синергичны и ведут к активации восстановительных процессов в тканях. Цель исследования - оценка терапевтической эффективности препарата Алфлутоп (К.О. Биотехнос С.А., Румыния) на модели открытого перелома бедренной кости у крыс. Методика. В области средней трети диафиза бедренной кости делали 2 расположенных перпендикулярно отверстия диаметром 1 мм, после чего перелом кости осуществляли вручную. Репозицию и фиксацию отломков осуществляли с помощью спиц Киршнера. Препарат (0,2 и 0,45 мл/кг) вводили внутримышечно, начиная с 1-х сут формирования патологии, на протяжении 20 сут. Эффективность препарата оценивали по особенностям формирования костной мозоли (рентгенологическое исследование) и скорости регенерации костной ткани (гистологическое исследование). Оценку проводили непосредственно после окончания терапии и через 2 нед после ее завершения. Результаты. Показано, что репаративный остеогенез был более выражен у животных, получавших препарат Алфлутоп. На фоне терапии в участке перелома возрастало число случаев перекрытия промежутка костной щели, а также статистически значимо увеличивалась площадь первичной костной мозоли. При гистологическом исследовании в участке перелома непосредственно после завершения терапии наблюдались признаки формирования хрящевой мозоли, а к исходу 2-й нед - костной мозоли с формированием костных балок, т. е. выявлялась отчетливая тенденция к активации репаративных процессов. Заключение. Использование препарата Алфлутоп в клинической практике целесообразно в качестве сопутствующей терапии при переломах костей.Aim. This study was designed to evaluate the therapeutic efficacy of Alflutop (К.О. Biotehnos С.А., Romania) using a rat model of femoral fracture. Methods. In the middle third region of the diaphysis of the femur, two perpendicular holes (diameter, 1 mm) were made, and the bone was manually broken. An intramedullary fixation was performed manually using a stainless Kirschner wire. Alflutop (0.2 and 0.45 ml/kg, i.m.) was injected into the rats daily for 20 days after the injury. The effect of Alflutop was evaluated immediately at the end of the treatment period and 2 weeks after the treatment completion using X-ray (callus formation) and histological data (bone regeneration). Results. The therapy resulted in some cases in partial bone fusion in the fracture line and significantly increased the area of cartilage callus. The most pronounced therapeutic effect was observed on day 35 of the experiment. Histological examination revealed signs of fracture healing in all experimental groups. Immediately after the therapy period, the formation of cartilage callus was observed in the fracture line. In 2 weeks after the therapy, signs of the formation of mineralized callus were noted. Along with the cartilaginous tissue, which was widely present, formation of trabecular bone and bone beams was observed. Two weeks after the therapy completion, the fracture healing process was more intensive in animals treated with Alflutop in either dose. Conclusion. The study confirmed that Alflutop can be used as a concomitant therapy for fracture healing in clinical practice.